Hidden danger
A "disguised" mutation can lead to miscarriage
Press Center of the Ministry of Education and Science
Scientists of the Research Institute of Medical Genetics of the Tomsk National Research Medical Center (NIMC) have identified a hidden mutation in the X chromosome that can lead to miscarriage or the development of a serious genetic disease in a child accompanied by mental retardation.
To find such a mutation, Tomsk geneticists conducted a study involving more than 300 women with miscarriage.
"We were wondering if the presence of a hidden mutation on the X chromosome could be the cause of miscarriage in healthy women. Usually, an equally probable inactivation of the X chromosome occurs in women: in half of the cells, the X chromosome obtained from the mother is active, in the other half — from the father. But in some situations, there is a shift when, for example, the X chromosome inherited from one of the parents is "turned off" in 90% of cells or more. In such cases, a woman may be a carrier of a mutation on the X chromosome and not suspect it, because the X chromosome with the mutation "does not work for her," comments Elizaveta Fonova, a junior researcher at the Ontogenetics laboratory of the Tomsk Research Institute of Medical Genetics.
According to the scientist, a third of the patients who had a significant deviation from the equally probable inactivation of the X chromosome did have microstructural chromosomal abnormalities on it. They did not manifest themselves in any way in these women, but they caused miscarriage and fetal death.
"The analysis of the nature of X-chromosome inactivation can be used as an additional test for women who are faced with the problem of miscarriage or have a child with a hereditary disease caused by mutations in the gene located on the X chromosome. In such cases, a woman may be a carrier of a pathogenic variant that does not affect her health due to selective inactivation, or the shutdown of such an X chromosome. However, when a mutation is transmitted to offspring, the variant may manifest itself as a hereditary disease, especially in sons with a single X chromosome of maternal origin, or lead to miscarriage," says Igor Lebedev, Deputy Director of the Tomsk NIMC for Scientific Work, Professor of the Russian Academy of Sciences, head of the Ontogenetics laboratory of the Tomsk NIMC Research Institute of Medical Genetics, Doctor of Biological Sciences.
In such cases, when planning the next pregnancy, a woman must be offered prenatal (prenatal) diagnosis. In case of mutations affecting the viability of the fetus, it is advisable to consider the possibility of using the method of in vitro fertilization (IVF) with preimplantation genetic testing. This approach will allow for embryo transfer without hereditary mutation on the X chromosome and wait for the onset of a healthy pregnancy.
A test for the presence of such a mutation can already be passed at the Research Institute of Medical Genetics of the Tomsk NIMC.
The results of the study are published in the journal Cytogenetic and Genome Research (Fonova et al., Skewed X-Chromosome Inactivation as a Possible Marker of X-Linked CNV in Women with Pregnancy Loss). The research was carried out with the support of the Ministry of Education and Science of the Russian Federation as part of the state task for conducting exploratory scientific research. (No. AAAAA-A20-120041390003-7)
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